Pharmacokinetic studies have been reported in human patients, with disseminated neoplasms refractory to conventional chemotherapy, who received gallium nitrate at doses of 600 mg/m.sup.2 intravenously in a phase I clinical trial; S. W. Hall, et al., Clin. Parmacol. Ther., Vol. 25, No. 1, pp. 82-87 (1979). In these reported studies gallium levels in biological fluids were analyzed by a modification of the colorimetric techniques of Willard and Fogg (J. Amer. Chem. Soc., Vol. 59, pp. 40-45 (1937)), which involved adding titanous chloride to the sample and extracting with isopropyl ether, and then allowing the isopropyl extract to react hydroxylamine hydrochloride and rhodamine B to obtain a colored gallium complex. The colored complex was extracted with toluene and absorbance at 565 nm was read with a spectrophotometer. It was reported that standard curves in plasma and urine were linear between concentrations of 1 and 60 micrograms/milliliter.
The pharmacokinetics of Gallium Nitrate in humans was also studied and reported by D. P. Kelsen, et al., Cancer, Vol. 46, pp. 2009-2013 (1980). Kelsen et al. assayed for gallium levels in plasma and urine by flameless atomic absorption spectrophotometry (AAS) using a PERKIN-ELMER 372 atomic absorption spectrophotometer. It was reported that gallium metal (500 mg) was dissolved in 5 ml of concentrated nitric acid and diluted with water to 1 liter, with standards being prepared daily by appropriate dilution. The working range was indicated to be 0.1-2.0 micrograms/ml for aqueous standards and 0.1-0.5 micrograms/ml, when 0.5N HNO.sub.3 or plasma were used as diluents. It was reported that gallium levels as low as 0.025 micrograms/ml were measurable in plasma treated and in urine diluted with 0.5N HNO.sub.3, and that sensitivity was decreased approximately five-fold in aqueous solutions of standards or urine.
Reed et al., Atomic Spectroscopy, Vol. 9, No. 3, pp. 93-95 (1988), reported that the ability to measure elemental platinum was enhanced by more than a log, using Atomic Absorption Spectroscopy methods with Zeeman background correction. In this respect, a series of tissue culture studies have been performed using cisplatin or carboplatin, using the method reported by Reed et al.